The following description is provided to assist the understanding of the reader. None of the information provided or references cited is admitted to be prior art to the present invention.
Transmissible spongiform encephalopathies (TSE) are untreatable and fatal neurodegenerative diseases that affect a number of mammalian species. Variants of TSE affect humans and many wild and domesticated animals. Examples of TSE are bovine spongiform encephalopathy (BSE) in cattle (also known as “mad cow disease”), scrapie in sheep, chronic wasting disease (CWD) in moose, deer and elk, and Creutzfeldt-Jakob disease (CJD) in humans. (Prusiner, Brain Pathol, 8:499-513 (1998).) All these diseases attack the neurological system and are characterized by initially long incubation followed by a short period of neurological symptoms, including dementia, loss of coordination, and eventually death.
The infectious agents that cause and transmit TSE are called prions. Prions are abnormally folded variants (PrPSc) of naturally occurring and normally harmless cellular proteins (PrPC). Prions are not believed to be associated with cells or virus particles, and most evidence shows that prions have no associated nucleic acids or other genetically transmissible material. In humans, the prion protein is encoded by the PRNP gene, which resides on chromosome 20. The protein is most commonly found in neurons, and in lower amounts in other cells such as leukocytes, monocytes, and platelets. (Holada et al., Lancet 356:1772 (2000).) When the normal cellular form of the prion protein is misfolded, the prion is able to infect and propagate by converting other normal molecules of the protein into the abnormally folded form. Thus, diseases caused by prions are characterized by accumulation of the misfolded form of the normal cellular prion protein. (Prusiner, PNAS, 95:13363-13383 (1998).) The misfolded form is extremely stable and accumulates as plaques in infected tissue, causing cell death and tissue damage that manifests as holes and a spongy appearance. The misfolded disease form of the prion protein is predominantly found in the brain, but has also been detected in the tonsil, spleen, and lymph nodes of infected humans.
Horizontal transmission is implicated in spreading the infectious agent causing scrapie in sheep and chronic wasting disease (CWD) in free-ranging cervids. (Hoinville, Rev Sci Tech, 15:827-852 (1996); Miller & Williams, Nature, 425:35-36 (2003).) The recent expansion of endemic regions of CWD in North America emphasizes the need to identify transmission routes. Several studies have advanced soil as a contributor to horizontal transmission, suggesting it acts as an environmental reservoir for retaining and facilitating exposure of susceptible animals to the infectious agent. (Johnson et al., PLoS Pathog, 2(4) (2006); Johnson et al., PLoS Pathog, 3(7) (2007), Seidel et al., PLoS ONE, 2(5) (2007).) TSE infectious agents can enter the soil environment from the decomposing carcasses of infected animals as well as from the excreta and saliva shed from infected animals. In addition, prion diseases can be transmitted by certain high-risk tissues, including the brain, spinal cord, cerebral spinal fluids, and the eye. After a surgical procedure on a prion-infected patient, or the butchering of a prion-infected animal, prion-containing residue may remain on the instruments and tools. During the long incubation period of prion-associated diseases, it is extremely difficult to determine if a person or animal is a prion carrier.
TSE infectious agents can survive in the environment for years (Seidel et al., PLoS ONE, 2(5) (2007)), subsequently serving as a long-term source of infection. Deer can become infected with CWD when exposed to facilities that previously contained decomposed infected carcasses and/or soil contaminated with excreta from infected animals. (Miller et al., Emerg Infect Dis, 10:1003-1006 (2004).) In addition, clay-bound prions are significantly more infectious than unbound PrPSc. (Johnson et al., PLoS Pathog, 2(4) (2006); Johnson et al., PLoS Pathog 3(7) (2007).)